DESCRIPTION Type two diabetes mellitus is a growing problem in the aging population, especially among Veterans. Currently, there is no effective therapy to prevent or reverse diabetic neuropathy. An ongoing clinical trial, Improving Neuropathy and Mobility in Subjects with Early Diabetes (INMED), funded by Rehabilitation R&D, will determine in a home based, tailored diet and physical activity program can prevent the progression of neuropathy and improve mobility in participants with impaired glucose regulation. The primary endpoints in this study are measurements of the intraepidermal nerve fiber density (IENFD) to measure the progression of neuropathy and a timed six-minute walk (6MW) as a measurement of the participants' mobility. Although the INMED study may show that a tailored lifestyle intervention (dietary advice, tailored exercise and mobility intervention) improves or prevents the progression of neuropathy, it is unknown if this benefit lasts beyond the period of the intervention and thus would have a sustained benefit to the subject. This information will be important in determining the long-term validity of the lifestyle intervention. The current study is a follow up study of the IMMED responders, defined as participants who had an improvement in the IENFD or 6MW compared to baseline. 48 subjects would be followed for an additional year without a specific intervention after the conclusion of the INMED study to see if there would be a sustained, long-term benefit of a tailored diet and exercise program on the progression of neuropathy and/or mobility as determined by the 6MW and the IENFD. The primary endpoint would be the 6MW at the conclusion of the additional year and the secondary endpoints would be the IENFD after the additional year and the 6MW after an additional 6 months. Information would also be collected to determine (1) if the participants continue to exercise without intervention, (2) if the amount o exercise decreases without ongoing counseling, (3) if they continue to maintain the same rate of improvement observed in the INMED study, and (4) if improvements in clinical measures of neuropathy are sustained beyond the INMED study. The applicant, Dr. Lindsay Zilliox, is an Assistant Professor in the Department of Neurology at the University of Maryland within two years of completing fellowship training who aims to become an independent VA clinical researcher. Her clinical training to this point has not included dedicated time for research training. This 2 year CDA-1 will allow her to complete coursework to earn a Master's of Science in Clinical Research through the University of Maryland, Baltimore. She will also continue to be mentored by a group of senior VA investigators that will provide a diverse research experience. Her primary mentor will be Dr. James Russell, who is a successful VA clinical researcher who shares a research interest in diabetic neuropathy and has worked with Dr. Zilliox over the past several years and co-authored three peer-reviewed journal articles with her. In addition she will gain experience and training in the field of mobility assessment and exercise interventions through mentorship from Dr. Neil Alexander. She will also gain expertise in the performance and interpretation of skin biopsies for the determination of intraepidermal nerve fiber density, which is essential in the field if peripheral neuropathy research. PUBLIC HEALTH RELEVANCE: Type two diabetes is a growing problem among all older adults, particularly Veterans. The majority of Veterans with diabetes are in poor physical health and they are significantly more impaired, with functional limitations, if they have neuropathy. An intervention with sustained, long-term benefits on two of the common disabilities associated with diabetes; mobility and neuropathy will potentially have major effects on health outcomes that are important to all older Veteran with diabetes. These outcomes include prevention of catastrophic diabetic complications, maintenance of personal independence, improved quality of life, and decreased costs for medical and personal care over time. If the proposed research determines that a lifestyle intervention has long term, sustained benefits on mobility and neuropathy progression as well as on levels of physical activity this intervention will be replicable and able to reach th large number of older Veterans with diabetes within the integrated VA Health System.